Diabetes Mellitus

1. Diabetes Mellitus Dr Mohamed El Houseny Shams

2. What is diabetes? • Diabetes mellitus (DM) is a chronic condition that is characterised by raised blood glucose levels (Hyperglycemia). 

3. Regulation of Plasma Glucose Level

4. How Insuline Decrease Plasma Glucose Level?

5. Classification of DM 1. Type 1 DM • It is due to insulin deficiency and is formerly known as. • Type I • Insulin Dependent DM (IDDM) • Juvenile onset DM 2. Type 2 DM • It is a combined insulin resistance and relative deficiency in insulin secretion and is frequently known as. • Type II • Noninsulin Dependent DM (NIDDM) • Adult onset DM

6. 3. Gestational Diabetes Mellitus (GDM): • Gestational Diabetes Mellitus (GDM) developing during some cases of pregnancy but usually disappears after pregnancy. 4. Other types: • Secondary DM

7. Etiology 1. Etiology of Type 1 Diabetes

9. 2. Etiology of Type 2 Diabetes

10. a

14. Characteristics Type 1 Type 2 % of diabetic pop 5-10% 90% Age of onset Usually < 30 yr + some adults Usually > 40 + some obese children Pancreatic function Usually none Insulin is low, normal or high Pathogenesis Autoimmune process Defect in insulin secretion, tissue resistance to insulin, increased HGO Family history Generally not strong Strong Obesity Uncommon Common History of ketoacidosis Often present Rare except in stress Clinical presentation moderate to severe symptoms: 3Ps, fatigue, wt loss and ketoacidosis Mild symptoms: Polyuria and fatigue. Diagnosed on routine physical examination Treatment Insulin, Diet Exercise Diet ,Exercise Oral antidiabetics,Insulin

15. Epidemiology • Type 1 DM • It is due to pancreatic islet β-cell destruction predominantly by an autoimmune process. • Usually develops in childhood or early adulthood • It accounts for upto 10% of all DM cases • Develops as a result of the exposure of a genetically susceptible individual to an environmental agent

16. Type 2 DM • It results from insulin resistance with a defect in compensatory insulin secretion. • Insulin may be low, normal or high! • About 30% of the Type 2 DM patients are undiagnosed (they do not know that they have the disease) because symptoms are mild. • It accounts for up to 90% of all DM cases

17. Risk Factors • Type 1 DM • Genetic predisposition • In an individual with a genetic predisposition, an event such as virusor toxin triggers autoimmune destruction of b-cells probably over a period of several years.

18. Risk Factors • Type 2 DM • Family History • Obesity • Habitual physical inactivity • Previously identified impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) • Hypertension • Hyperlipidemia

20. Carbohydrate Metabolism • Carbohydrates are metabolized in the body to glucose. • CNS uses glucose as its primary energy source. This is independent of insulin. • Glucose is taken by the muscle to produce energy (insulin required). • Glucose is stored in the liver as glycogen and in adipose tissues as fat. • Insulin is produced and stored by the β-cells of the pancreas

21. Carbohydrate Metabolism (Cont’d) • Postprandial glucose metabolism in normal individuals: • After food is ingested, blood glucose concs rise and stimulate insulin release. • Insulin action: • glucose uptake by the tissues • liver glycogen formation and glycogen breakdown • lipid synthesis and inhibits fatty acid breakdown to ketone bodies • Promotes protein synthesis

22. Carbohydrate Metabolism (Cont’d) • Fasting glucose metabolism in normal individuals: • In the fasting state, insulin release is inhibited. • Hormones that promote an increase in blood glucose are released: • Glucagon, epinephrine, growth hormone, glucocorticoids, and thyroid hormones. • Glycogenolysis • Gluconeogenesis: AA are transported from muscle to liver and converted to glucose. • TG are broken down into free FAs as an alternative fuel source.

23. Pathophysiology • Type 1 DM • Type 1 DM is characterized by an absolute deficiency of insulin due to immune- mediated destruction of the pancreatic b-cells • In rare cases the b-cell destruction is not due to immune mediated reaction (idiopathic type 1 DM)

25. Pathophysiology • Type 1 DM • There are four stages in the development of Type 1 DM: • Preclinical period with positive b-cell antibodies • Hyperglycemia when 80-90% of the β- cells are destroyed. • Transient remission (honeymoon phase). • Establishment of the disease

26. Pathophysiology Birth Time (years)

27. Pathophysiology • Type 2 DM • Type 2 DM is characterized by the presence of both insulin resistance (tissue insensitivity) and some degree of insulin deficiency or b- cell dysfunction • Type 2 DM occurs when a diabetogenic lifestyle (excessive calories, inadequate caloric expenditure and obesity) is superimposed upon a susceptible genotype

28. Pathophysiology • Type 2 DM • 300 • 250 • 200 • 150 • 100 • 50 • 0 • Glucose • mg/dL • Fasting blood glucose • Post-meal glucose • Relative • b- cell • Function • % • 250 • 200 • 150 • 100 • 50 • 0 • b-cell failure • Years of diabetes

29. Laboratory Tests 1. Glucosuria • To detect glucose in urine by a paper strip • Semi-quantitative • Normal kidney threshold for glucose is essential • 2. Ketonuria • To detect ketonbodies in urine by a paper strip • Semi-quantitative

30. Laboratory Tests (Cont’d) 3. Fasting blood glucose • Glucose blood concentration in samples obtained after at least 8 hours of the last meal • 4. Random Blood glucose • Glucose blood concentration in samples obtained at any time regardless the time of the last meal

31. Laboratory Tests (Cont’d) 5. Glucose tolerance test • 75 gm of glucose are given to the patient with 300 ml of water after an overnight fast • Blood samples are drawn 1, 2, and 3 hours after taking the glucose • This is a more accurate test for glucose utilization if the fasting glucose is borderline

32. Laboratory Tests (Cont’d) 6. Glycosylated hemoglobin (HbA1C) • HbA1C is formed by condensation of glucose with free amino groups of the globin component of hemoglobin • Normally it comprises 4-6% of the total hemoglobin. • Increase in the glucose blood concentration increases the glycated hemoglobin fraction. • HbA1C reflects the glycemic state during the preceding 8-12 weeks.

33. Laboratory Findings (Cont’d) 7. Serum Fructosamine • Formed by glycosylation of serum protein (mainly albumin) • Since serum albumin has shorter half life than hemoglobin, serum fructosamine reflects the glycemic state in the preceding 2 weeks • Normal is 1.5 - 2.4 mmole/L when serum albumin is 5 gm/dL.

34. Self Monitoring Test • Self-monitoring of blood glucose • Extremely useful for outpatient monitoring specially for patients who need tight control for their glycemic state. • A portable battery operated device that measures the color intensity produced from adding a drop of blood to a glucose oxidase paper strip. • e.g. One Touch, Accu-Chek, DEX, Prestige and Precision.

36. Diagnostic Criteria • Any one test should be confirmed with a second test, most often fasting plasma glucose (FPG). • This criteria for diagnosis should be confirmed by repeating the test on a different day.

38. Clinical Presentation • Type 2 DM • Patients can be asymptomatic • Polyuria • Polydipsia • Polyphagia • Fatigue • Weight loss • Most patients are discovered while performing urine glucose screening • Type 1 DM • Polyuria • Polydipsia • Polyphagia • Weight loss • Weakness • Dry skin • Ketoacidosis

39. Treatment Desired outcome • Relieve symptoms • Reduce mortality • Improve quality of life • Reduce the risk of microvascular and macrovascular disease complications • Macrovascular complications: Coronary heart disease, stroke and peripheral vascular disease • Microvascular Complications: Retinopathy, nephropathy and neuropathy

40. Treatment How to achieve the goals ? • Near normal glycemic control reduce the risk of developing microvascular disease complications • Control of the traditional CV risk factors such as smoking, management of dyslipidemia, intensive BP control and antiplatelet therapy.

41. TreatmentGeneral approaches • Medications • Dietary and exercise modification • Regular complication monitoring • Self monitoring of blood glucose • Control of BP and lipid level

42. TreatmentGlycemic goals

43. Treatment Complication monitoring • Annual eye examination • Annual microalbuminuria • Feet examination • BP monitoring • Lipid profile

44. Treatment Self-monitoring of blood glucose • Frequent self monitoring of blood glucose to achieve near normal level • More intense insulin regimen require more frequent monitoring

45. Treatment Nonpharmacological therapy • For type 1 the goal is to regulate insulin administration with a balanced diet • In most cases, high carbohydrate, low fat, and low cholesterol diet is appropriate • Type 2 DM patients need caloric restriction Diet

46. Treatment Nonpharmacological therapy Diet (Cont’d) • Artificial sweeteners: • e.g. Aspartame, saccharin, sucralose, and acesulfame • Safe for use by all people with diabetes • Nutritive sweeteners: • e.g. fructose and sorbitol • Their use is increasing except for acute diarrhea in some patients

47. TreatmentNonpharmacological therapy • Exercise improves insulin resistance and achieving glycemic control. • Exercise should start slowly for patients with limited activity. • Patients with CV diseases should be evaluated before starting any exercise Activity

49. TreatmentPharmacological therapy • Insulin (Type 1 and Type 2 DM) • Sulfonylurea (Type 2 DM) • Biguanides (Type 2 DM) • Meglitinides (Type 2 DM) • Thiazolidinediones Glitazones (Type 2 DM) • a-Glucosidase inhibitors (Type 2 DM)

50. Pharmacological Treatment of Type 2 DM Strategy for Controlling Hyperglycemia Biosynthesis in Liver Absorption from Diet a-Glucosidase Inhibitors Biguanides Cellular Uptake Serum Sugar Biguanides; thiazolidinediones Pancreas Insulin Sulfonylureas Meglitinide